Histidine-rich glycoprotein (HRGP), a plasma protein with anti-heparin and anti-fibrinolytic activity, has been associated with thrombophilia in three families. Therefore, it may promote hyper-coagulability. The following objectives have been achieved in the laboratory: purification of HRGP, using a combination of cobalt-sepharose, and development of an enzyme-linked immunosorbent assay for its quantitation. We have confirmed HRGP's anti-heparin activity and demonstrated that it binds to plasminogen. An ongoing project is the study of HRGP binding to proteins that contain a "kringle" structure. By identifying binding sites for HRGP, we hope to discover potential functions for this protein.